crossing96/oncoscreening huggingface dataset:
4-Hydroxybutyl(butyl)nitrosamine-induced urinary bladder cancers in mice: characterization of FHIT and survivin expression and chemopreventive effects of indomethacin.	The administration of 4-hydroxybutyl(butyl)nitrosamine (OH-BBN) to male B6D2F1 mice yielded a high incidence of large palpable urinary bladder cancers. Since prior studies demonstrated chemopreventive effects of non-steroidal anti-inflammatory drugs (NSAIDs), we further explored the efficacy of the NSAID indomethacin using different treatment regimens. OH-BBN was administered twice per week for 12 weeks (the first week of treatment was designated week 1). In Experiment I continual indomethacin treatment (20 mg/kg diet) was initiated either prior to (week -1) or following (week 13) OH-BBN dosing. Palpable bladder masses (subsequently diagnosed as cancers) developed in 32% of carcinogen-treated only mice by 32 weeks, while mice administered indomethacin either prior to or after OH-BBN developed palpable masses in 3 and 6% of the animals, respectively. In Experiment II mice were treated with indomethacin beginning 1 week after OH-BBN for either 12 weeks (limited treatment, weeks 13-24) or for 30 weeks (weeks 13-42). Continual treatment resulted in a 77% decrease in palpable bladder masses and an 82% decrease in all cancers (palpable and microscopic), while limited treatment decreased palpable masses by 48% but failed to decrease the number of bladder cancers (palpable plus microscopic). In Experiment III OH-BBN-treated mice were followed for 61 weeks. Palpable masses developed in 66% of control mice, while 26% of mice treated with indomethacin continually from 1 week after OH-BBN (weeks 13-61) developed palpable masses. A separate group in this study treated with indomethacin beginning when 5% of the mice had palpable bladder masses continued to develop new masses for an additional 4 weeks. By 6 weeks after beginning indomethacin treatment, however, these animals showed a profound decrease in the development of additional cancers. The expressions of FHIT and survivin in normal urinary bladder epithelium and in bladder cancers were determined by immunohistochemical analysis. FHIT was expressed at high levels in normal epithelium, but was minimally expressed in cancers, and even showed decreased expression in papillomas. The anti-apoptotic protein survivin was not expressed in normal bladder epithelium, but was variably expressed in cancers. FHIT and survivin expressions were similar in cancers from indomethacin-treated and non-treated mice.	bladder
Deletions of p15 and p16 in schistosomal bladder cancer correlate with transforming growth factor-alpha expression.	OBJECTIVES: Cell proliferation is stimulated by growth factors and inhibited by p15 and p16 gene products. We compared cell regulators, TGF-alpha, p15, and p16, in schistosomal and non-schistosomal bladder cancer to explore possible differences in their alterations between the two subtypes and their correlations with proliferation pattern [synthetic phase fraction (SPF)], DNA ploidy, and clinicopathological factors. METHODS: Tumor tissue samples were obtained from 120 patients. Expressions of p15 and p16 genes were investigated by the polymerase chain reaction, while TGF-alpha protein expression was measured by an enzyme immunoassay (EIA) method. RESULTS: Deletion of both p15 and p16 was observed in 62 and 46 bladder tumors, respectively. TGF-alpha was overexpressed in 64 bladder tumors. A highly significant association was observed between the two deleted genes and TGF-alpha positivity. Of the entire group, p15 and p16 alteration and positive TGF-alpha (> or =cutoff value) were significantly expressed in schistosomal bladder cancer (68.1%, 60.9%, and 65.2%), and squamous cell carcinoma type (SCC) (69.1%, 64.7% and 72.1%) compared to those with non-schistosomal bladder cancer (29.4%, 7.8%, and 37.3%) or transitional cell carcinoma (TCC) (28.8%, 3.8%, and 28.8), respectively. A significant association between p15 and p16 deletion and TGF-alpha positivity with high SPF, aneuploid DNA pattern, late stages, and high histological grades was also documented. CONCLUSION: Alteration of p15 and p16 genes and overexpression of TGF-alpha appears to be an event in bladder cancer that occurs more frequently in schistosomal bladder cancer and SCC, and may play an important role in their development. These observations may provide insight into treatment guided by molecular changes.	bladder
Expression of HER3, HER4 and their ligand heregulin-4 is associated with better survival in bladder cancer patients.	The epidermal growth factor system has been associated to prognosis in patients with bladder cancer based mainly on the expression of the epidermal growth factor (EGF) receptor 1 (EGFR) and HER2 and their activating ligands. Since limited information exists concerning the expression of other parts of the EGF system, we examined the expression of the receptors HER3 and HER4 and their activating ligands, the heregulins (HRGs), in bladder cancer patients. Biopsies from bladder cancer tumours were obtained from 88 patients followed for a median of 23 months (range, 1-97 months). The mRNA content of four ligands and their isoforms (HRG1alpha, HRG1beta, HRG2alpha, HRG2beta, HRG3 and HRG4) and two receptors (HER3 and HER4) was quantified by real-time PCR. A significantly lower mRNA expression level of HER3 (P=0.0003), HRG2alpha (P=0.0159), HRG2beta (P=0.0007) and HRG4 (P<0.0001) was observed in muscle-invasive (T2-T4) tumours as compared to superficial (Ta) tumours. The expression of HER3 mRNA correlated strongly to overall survival (P=0.0042); increased expression of HER4 (P=0.0261) and HRG4 (P=0.0245) was also associated with better prognosis. Interestingly, patients with coexpression of HER3 (P=0.0034) or HER4 (P=0.0080) together with their stimulating ligand HRG4 showed even better survival than for HER3 or HER4 alone. Our results together with previous data suggest a dual face for the EGF system. While it is well established that an increased signalling through HER1 and HER2 is related to a poor prognosis, our data suggest that signalling through HER3 and HER4 is related to a favourable outcome in bladder cancer patients.	bladder
Deletions of chromosomes 9 and 8p in histologically normal urothelium of patients with bladder cancer.	"OBJECTIVES: Multifocality and frequent recurrence of urothelial carcinoma of the urinary bladder indicate a disease of the entire ""urothelial field"", but little is known about chromosomal alterations in histologically normal urothelium. Histopathologically normal urothelium from patients with and without concurrent urothelial carcinoma was analyzed for loss of heterozygosity (LOH) on chromosomes 8p, 9 and 17p, regions that are known to play an important role in urothelial carcinogenesis. MATERIALS AND METHODS: Histologically inconspicuous urothelial mucosa samples (n = 160) from cystectomy specimens of patients with urothelial carcinoma (n = 15, max. diagnosis: CIS, pT1-4; all tumors grade 3) were studied. Control samples (n = 50) were obtained from patients with benign prostatic hyperplasia (n = 30) and from cystectomies performed for invasive non-urothelial carcinoma (n = 20). Tissue samples were laser-microdissected and DNA was isolated using standard protocols. LOH analyses were performed using 16 polymorphic markers on chromosomes 8p, 9p/q and 17p. RESULTS: All investigated samples were informative for at least one microsatellite marker on each chromosome/chromosomal arm. Deletions were found on chromosome 9 and/or 8p in 15/160 (9.4%) of normal urothelial samples from urothelial cancer patients. These alterations were only found in 5/15 patients with urothelial carcinoma. There were no deletions on chromosome 17p. The marker D9S1113 on chromosome 9q33-34 was most frequently affected (11/15 samples, 73%). No chromosomal deletions were found in any of the 50 urothelial control samples. CONCLUSION: Specific genetic alterations frequently associated with bladder cancer are detectable in histologically normal urothelium of patients with bladder cancer, supporting the field effect hypothesis in urothelial carcinogenesis. However, intramucosal spread of tumor cells that escape light microscopic detection remains a possibility, since normal urothelium and concurrent carcinomas showed matching deletions. Chromosomal deletions in normal bladder mucosa are not a common finding and argue against a frequent genomic alteration of the entire urothelial field in bladder carcinogenesis."	bladder
Postoperative management and rehabilitation of patients receiving an ileal orthotopic bladder substitution.	Ileal orthotopic bladder substitution has become one of the main therapeutic options following radical cystectomy for invasive bladder cancer. While careful patient selection and the surgical technique are necessary to obtain good long-term results and a satisfactory quality of life, postoperative management is also of utmost importance. It includes successful voiding rehabilitation (micturition technique, complete bladder emptying, increase of functional reservoir capacity, and sphincter training) and a meticulous lifelong followup.	bladder
Paclitaxel-loaded gelatin nanoparticles for intravesical bladder cancer therapy.	PURPOSE: The present report describes the development of paclitaxel-loaded gelatin nanoparticles for use in intravesical therapy of superficial bladder cancer. The commercial formulation of paclitaxel contains Cremophor, which forms micelles and thereby entraps the drug and reduces its partition across the urothelium. EXPERIMENTAL DESIGN: Paclitaxel-loaded gelatin nanoparticles were prepared using the desolvation method, and their physicochemical and biological properties were characterized. RESULTS: The size of the particles ranged from 600 to 1,000 nm and increased with the molecular weight of the gelatin polymer. Under optimal conditions, the yield was >80%, and the drug loading was 0.7%. Wide-angle X-ray diffraction analysis showed that the entrapped paclitaxel was present in an amorphous state, which has higher water solubility compared with the crystalline state. Identical, rapid drug release from nanoparticles was observed in PBS and urine, with approximately 90% released at 37 degrees C after 2 hours. Treatment with a protease (i.e., Pronase) rapidly degraded the nanoparticles, with half-lives of 23.8 minutes, 0.6 minute, and 0.4 minute in the presence of 0.01, 0.05, and 0.25 mg/mL Pronase, respectively. The paclitaxel-loaded nanoparticles were active against human RT4 bladder transitional cancer cells; the IC50 paclitaxel-equivalent concentrations were nearly identical to those of aqueous solutions of paclitaxel, i.e., approximately 30 nmol/L (equivalent to approximately 25 ng/mL) for 2-hour treatments and approximately 4 nmol/L for 96-hour treatments. In dogs given an intravesical dose of paclitaxel-loaded particles, the drug concentrations in the urothelium and lamina propria tissue layers, where Ta and T1 tumors would be located, were 7.4 +/- 4.3 mug/g (mean +/- SD; 3 dogs; 9 tissue sections), which were 2.6x the concentrations we reported for dogs treated with the Cremophor formulation. CONCLUSIONS: Paclitaxel-loaded gelatin nanoparticles represent a rapid release, biologically active paclitaxel formulation that can be used for intravesical bladder cancer therapy.	bladder
Detection of methylated apoptosis-associated genes in urine sediments of bladder cancer patients.	PURPOSE: There is increasing evidence for a fundamental role for epigenetic silencing of apoptotic pathways in cancer. Changes in DNA methylation can be detected with a high degree of sensitivity, so we used the MethyLight assay to determine how methylation patterns of apoptosis-associated genes change during bladder carcinogenesis and whether DNA methylation could be detected in urine sediments. EXPERIMENTAL DESIGN: We analyzed the methylation status of the 5' regions of 12 apoptosis-associated genes (ARF, FADD, TNFRSF21, BAX, LITAF, DAPK, TMS-1, BCL2, RASSF1A, TERT, TNFRSF25, and EDNRB) in 18 bladder cancer cell lines, 127 bladder cancer samples, and 37 samples of adjacent normal bladder mucosa using the quantitative MethyLight assay. We also analyzed the methylation status in urine sediments of 20 cancer-free volunteers and 37 bladder cancer patients. RESULTS: The 5' regions of DAPK, BCL2, TERT, RASSFIA, and TNFRSF25 showed significant increases in methylation levels when compared with nonmalignant adjacent tissue (P < or = 0.01). Methylation levels of BCL2 were significantly associated with tumor staging and grading (P < or = 0.01), whereas methylation levels of RASSF1A and ARF were only associated with tumor stage (P < or = 0.04), and TERT methylation and EDNRB methylation were predictors of tumor grade (P < or = 0.02). To investigate clinical usefulness for noninvasive bladder cancer detection, we further analyzed the methylation status of the markers in urine samples of patients with bladder cancer. Methylation of DAPK, BCL2, and TERT in urine sediment DNA from bladder cancer patients was detected in the majority of samples (78%), whereas they were unmethylated in the urine sediment DNA from age-matched cancer-free individuals. CONCLUSIONS: Our results indicate that methylation of the 5' region of apoptosis-associated genes is a common finding in patients with bladder carcinoma. The ability to detect methylation not only in bladder tissue, but also in urine sediments, suggests that methylation markers are promising tools for noninvasive detection of bladder cancers. Our results also indicate that some methylation markers, such as those in regions of RASSF1A and TNFRSF25, might be of limited use for detection because they are also methylated in normal bladder tissues.	bladder
Dermatofibrosarcoma protuberans of the urinary bladder: a case report.	The Authors reported a case of dermatofibrosarcoma protuberans of the urinary bladder in a 17-year old boy. The biology of this unusual urinary tumor is discussed.	bladder
[Establishment of immortalized cell line BLTR-4 and primary identification of its biological character].	OBJECTIVE: To establish immortalized cell line from the urothelium of the urinary bladder and identify the characteristics of the cell line. METHODS: Human papillomavirus 16 (HPV-16) plasmid was used to transfect urothelium of infant urinary bladder in vitro with the help of Fugene-6, and this plasmid contained E6 and E7 genes of HPV-16. We also identified the existence of HPV-16 E6 and E7 genes and the biological characteristics of the cell line by PCR, immunohistochemistry, and the biology identification. RESULTS: BLTR-4 cell line, produced from the transfection of HPV-16K plasmid, was a cell line from urothelium with the expression of HPV-16 E6 and E7 genes. It had been cultured more than 70 passages, and the characteristics of growth was similar to the immortalized cell line as reported. CONCLUSIONS: BLTR-4 cell line is an immortalized cell line from urothelium of the urinary bladder, which contains HPV-16 E6 and E7 genes. BLTR-4 cell line is a good experimental model to investigate the relationship of the infection of high risk HPV and transitional cell carcinoma (TCC) in vitro.	bladder
Multiple mechanisms downregulate CDKN1C in human bladder cancer.	Expression of the imprinted CDKN1C gene at chromosome 11p15.5 encoding the cell cycle inhibitor p57(KIP2) is disturbed in Beckwith-Wiedemann syndrome and in several human cancers by different mechanisms. Many advanced urothelial cancers (TCC) display downregulation of CDKN1C expression. The responsible mechanisms were investigated in TCC cell lines, with cultured normal urothelial cells (UEC) as controls. CDKN1C mRNA expression was diminished in 12/15 TCC lines and p57(KIP2) protein was decreased accordingly. Because CDKN1C is expressed from the maternal allele only, LOH at 11p15.5 represents one mechanism of downregulation. In 3 cell lines, several polymorphic markers flanking CDKN1C were homozygous compatible with this mechanism. Hypermethylation of the CDKN1C promoter, a reported cause of downregulation in other cancers, was detected by bisulfite sequencing in several cell lines and appeared associated with downregulation in at least one cell line. The methylation inhibitor 5-aza-2'deoxycytidine induced CDKN1C expression in this cell line and others. A third reported mechanism involves a switch of both alleles toward a paternal imprinting pattern, indicated by hypomethylation of a differentially methylated region (DMR) in the imprinting center (IC2). This hypomethylation was detected in most TCC lines, and was associated with re-expression of the non-coding LIT1 RNA and with downregulation of CDKN1C in several. Thus, CDKN1C downregulation in TCC seems to occur by several different mechanisms. This finding and the ability of p57(KIP2) to induce senescence in urothelial cells make CDKN1C a good candidate for a tumor suppressor at 11p in TCC.	bladder
Current status of radiation therapy and combined-modality treatment for bladder cancer.	BACKGROUND: Standard treatment for muscle-invasive bladder cancer is radical cystectomy. Combined-modality treatment (CMT), including transurethral resection (TURBT), radiation therapy (RT) and systemic chemotherapy, has been shown to produce survival rates comparable to those of radical cystectomy. With these programs, cystectomy has been reserved for patients with incomplete response or local relapse after trimodality treatment. METHODS: This review summarizes series of radical RT with different fractionation schedules and focuses on CMT for muscle-invasive bladder cancer. Current protocols of the bladder-sparing approach will be discussed and the background of future developments, including incorporation of promising new chemotherapeutic agents as well as the role of predictive and prognostic factors in selecting patients for the respective treatment alternatives, will be given. RESULTS: There is moderate evidence that hyperfractionated and accelerated regimens are superior to conventional RT at least in situations where no concomitant chemotherapy is applied. Several phase II studies and one phase III study indicate that concomitant radiochemotherapy is superior to RT alone. In modern series of CMT, 5-year survival rates in the range of 50-60% have been published, and about three quarters of the surviving patients maintained their own bladder. Recent data suggest that incorporation of newer chemotherapeutic agents, particularly gemcitabine and taxanes, in CMT protocols is feasible and promising. Clinical criteria helpful in determining patients for bladder preservation include such variables as early tumor stage, unifocal tumor, a visibly and microscopically complete TURBT, and absence of ureteral obstruction. CONCLUSION: CMT for bladder cancer is a reasonable treatment option for patients who are deemed medically unfit for cystectomy and for those seeking an alternative to radical cystectomy.	bladder
Synergistic effects of Cox-1 and -2 inhibition on bladder and prostate cancer in vitro.	BACKGROUND: We hypothesized that combined treatment with cyclooxygenase (Cox)-1 (catechin) and Cox-2 (NS398)-specific inhibitors would reduce cellular proliferation synergistically in genitourinary cancer. METHODS: Bladder (T24 and TCCSUP) and prostate (DU145, LnCaP, and PC3) cancer cell lines were treated with catechin and NS398 at a dose of 100 mumol/L as single and combined treatments. Viability was measured by MTT assay at 24 and 72 hours. RESULTS: Significant synergism of Cox-1 and Cox-2 inhibitors was observed in both bladder cancer lines at both 24 and 72 hours. Synergism of Cox-1 and -2 inhibitors also was noted in the DU145 cells at 72 hours, LnCap cells at 24 hours, and PC3 at both 24 and 72 hours. CONCLUSIONS: Significant synergistic effects exhibited by the combination of Cox-1 and Cox-2 inhibitors suggest that these could become a highly effective treatment modality for carcinoma of both the bladder and prostate.	bladder
Prostatic capsule- and seminal-sparing cystectomy for bladder carcinoma: initial results for selected patients.	OBJECTIVE: To evaluate the oncological outcome and functional results of prostate-sparing cystectomy (PSC), proposed for treating bladder cancer, used since 1999 in our institution in an attempt to preserve male sexuality and to increase continence after cystectomy. PATIENTS AND METHODS: Between January 1999 and December 2001, 111 men were candidates for cystectomy; 42 were selected for a prostatic capsule- and seminal-sparing cystectomy with orthotopic urinary diversion. All patients had clinically organ-confined tumours (clinical stage </= T2, N0M0). The first stage of the procedure was a transurethral resection of the prostate to exclude the involvement of transitional cell carcinoma (TCC) in the prostate. RESULTS: Eight patients were excluded from PSC because they had TCC (seven) or prostate adenocarcinoma (one). The mean age of the remaining 34 patients was 61 years and all underwent PSC. After a mean follow-up of 26 months, seven patients (21%) had a recurrence; one developed a local recurrence, there were widespread metastases in six (18%), and five had histologically confirmed organ-confined tumour (T1-2N0M0). Rates for daytime and night-time continence were 90% and 85%, and in 29 patients potency was unchanged. CONCLUSION: These early results suggest that PSC is not equivalent to radical cystoprostatectomy for bladder cancer control, despite marked improvements in the functional results. Moreover, in carefully selected patients this approach appears to dramatically increase an unusually high metastasis rate. Therefore, the indications for PSC should be either clearly well defined or abandoned in these patients.	bladder
Relation between serum anti-p53 antibodies and microvessel density in bladder cancer patients.	INTRODUCTION: Etiology of serum anti-p53 antibodies in bladder cancer patients is still unknown. In this study we evaluated the relationship between serum anti-p53 antibodies and microvessel density in bladder cancer patients. MATERIALS AND METHODS: Seventy-six patients with transitional cell carcinoma of the urinary bladder were assessed prospectively (18 Ta, 30 T1, 28 T2>or =). Serum anti-p53 antibodies were detected by enzyme-linked immunosorbent assay. Tumor p53 overexpression was assessed by immunohistochemical staining. Vessels were stained immunohistochemically using an antibody against platelet endothelial cell-adhesion molecule CD31. Spearman correlation test and t test were used for statistical analysis. RESULTS: Serum anti-p53 antibodies were positive in 25 (60%) of 41 tumor p53-positive patients. While the mean (SD, range) microvessel density was found to be 43 (7.59, 8-99) in patients who had positive serum anti-p53 antibodies, it was found to be 23 (4.53, 6-98) in patients who had negative serum anti-p53 antibodies. There was a good correlation between serum anti-p53 antibodies and microvessel density (p<0.05). No correlation was found between tumor p53 expression and microvessel density (p>0.05). CONCLUSIONS: We found that there is a significant correlation between the microvessel density and serum anti-p53 antibodies. This result may show the role of angiogenesis in the etiology of serum anti-p53 antibodies in bladder cancer patients.	bladder